Effect of Intralipid on hypoxic and angiotensin-II induced pulmonary vasoconstriction in the isolated rat lung
Related Experiment Videos
S V Baudouin1, M Messent, T W Evans
1Department of Anaesthesia and Intensive Care, National Heart and Lung Institute, Royal Brompton and National Heart and Lung Hospital, London, UK.
Objective:
Lipid infusions are reported to cause hypoxemia by increasing intrapulmonary shunt fraction. However, the mechanism by which they worsen gas exchange is unknown. We hypothesized that a reduction in hypoxic pulmonary vasoconstriction, caused by lipid infusion, could be the cause of increased shunt.
Design:
A prospective, controlled laboratory study.
Setting:
A postgraduate teaching hospital laboratory.
Subjects:
Male Wistar rats weighing 250 to 300 g.
Interventions:
Four separate series of experiments were performed: a) The pulmonary vasopressor response to angiotensin-II was compared before and after adding either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). b) The pulmonary vasopressor response to hypoxia (FIO2 of 0.3) was compared before and after either 0.9% sodium chloride (control n = 5) or 20 microL of Intralipid (n = 8). c) 1 microM of indomethacin was added before either 0.9% sodium chloride (control n = 5) or Intralipid (n = 5) and the hypoxic pulmonary vasoconstriction response was compared. d) 10(-3) M L-monomethyl-n-arginine was added before 20 microL of Intralipid and the hypoxic pulmonary vasoconstriction response was compared (n = 5).
Measurements And Main Results:
Changes in pulmonary arterial pressure were measured before and after interventions. Intralipid reduced the angiotensin-II pressor response by 36 +/- 3% (p = .005) and the hypoxic pulmonary vasoconstriction response by 50 +/- 2% (p = .0003). This action was not blocked by pretreatment with either indomethacin or L-monomethyl-n-arginine.
Conclusions:
Intralipid reduces the hypoxic pulmonary vasoconstriction response in the isolated, blood perfused rat lung. This action is nonspecific, as shown by a similar reduction in the pulmonary pressor response to angiotensin-II. Pharmacologic blockade of prostaglandin release, by indomethacin, and nitric oxide release, by L-monomethyl-n-arginine did not prevent the reduction in hypoxic pulmonary vasoconstriction, thereby suggesting that neither agent mediates the lipid-induced change in pulmonary vasoreactivity.